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Subjects

Abstract

Metastatic disease is the principal cause of prostate-cancer-related mortality. Our ability to accurately recapitulate the spread of prostate cancer to bone — the most common site of metastasis — is critical to the development of novel metastasis-directed therapies. Several translational models of prostate cancer bone metastasis have been developed, including animal models, cell line injection models, 3D in vitro models, bone implant models, and patient-derived xenograft models. The use of these models has led to numerous advances in elucidating the molecular mechanisms of metastasis and innovations in targeted therapy. Despite this progress, current models are limited by a failure to holistically reproduce each individual element of the metastatic cascade in prostate cancer bone metastasis. In addition, factors such as accurate recapitulation of immunobiological events and improvements in tumour heterogeneity require further consideration. Knowledge gained from historical and currently used models will improve the development of next-generation models. An introspective appraisal of current preclinical models demonstrating bone metastases is warranted to narrow research focus, improve future translational modelling, and expedite the delivery of urgently needed metastasis-directed treatments.

Key points

The development of novel metastasis-directed prostate cancer therapies is highly reliant on our ability to accurately reproduce the underlying mechanisms in vivo.

Ben-David, U. et al. Patient-derived xenografts undergo mouse-specific tumor evolution. Nat. Genet.49, 1567–1575 (2017). This is a critical look into the stability of the heterogeneity of PDX tumours that are serially propagated in mice.

Koh, A. J. et al. Cells of the osteoclast lineage as mediators of the anabolic actions of parathyroid hormone in bone. Endocrinology146, 4584–4596 (2005). In this article, Koh et al. describe the method to transplant mouse vossicles into host mice, paving the way for a novel bone implant model of prostate cancer.

Wang, N. et al. The frequency of osteolytic bone metastasis is determined by conditions of the soil, not the number of seeds; evidence from in vivo models of breast and prostate cancer. J. Exp. Clin. Cancer Res.34, 124 (2015).